The production of progesterone by the corpus luteum is crucial to prepare the endometrium for implantation and for the maintenance of pregnancy. Recent investigations have revealed that progesterone can acts also in luteal cells to sustain its own production through an intracrine mechanism, despite the lack of progesterone receptor in the rat corpus luteum. Signaling occurs through the glucocorticoid receptor. The lack of progesterone receptor is puzzling since the expression of this gene is increased by estradiol, and since the rat corpus luteum produces estradiol, expresses estrogen receptors, and is highly responsive to estradiol. Studies performed in both laboratories involved in the proposed study, have demonstrated that progesterone sustains its own production by preventing the expression of at least two gene products: 20alpha-hydroxysteroid dehydrogenase, an enzyme which catabolizes progesterone; and interleukin-6, a cytokine detrimental for steroidogenesis. The overall aims of this proposal are: 1) to determine the reason by which the progesterone receptor is silenced in the rat corpus luteum; 2) to examine the molecular mechanisms whereby progesterone down regulates the expression of luteal 20alpha- hydroxysteroid dehydrogenase; and 3) to determine whether the inhibition of interleukin-6 expression by progesterone in the corpus luteum involves the nuclear factor kappa-B (NF-kappaB) family of transcription factors.